Polycyclic 2- aminothiazole systems, processes for their...

Details Polycyclic 2- aminothiazole systems, processes for their... Polycyclic 2- aminothiazole systems, processes for their...

2000-02-10

2001-06-26

Stockton, Laura L. (Department: 1626)

Drug, bio-affecting and body treating compositions

Designated organic active ingredient containing

Having -c-, wherein x is chalcogen, bonded directly to...

C514S366000, C546S270100, C548S150000

Reexamination Certificate

active

06251922

ABSTRACT:

BACKGROUND OF THE INVENTION
The invention relates to polycyclic 2-aminothiazole systems and their physiologically tolerated salts and physiologically functional derivatives.
2-Aminothiazole systems are described as anti-inflammatory substances in R. Gupta et al., Indian J. Pharm. Sci. 1991, 53, 245-248.
The invention was based on the object of providing compounds which display a therapeutically utilizable anorectic effect.
SUMMARY OF THE INVENTION
The invention relates to compounds of the formula I
in which
Y is a direct linkage, CH
2
or CH
2
—CH
2
;
X is CH
2
or O;
R1 is CF
3
, CN, COOH, COO(C
1
-C
6
)alkyl, CONH
2
, CONH(C
1
-C
6
) alkyl, CON[(C
1
-C
6
)alkyl]
2
, (C
1
-C
6
)-alkyl, (C
2
-C
6
)-alkenyl, (C
2l-C
6
)-alkynyl, O—(C
1
-C
6
)-alkyl (where one, more than one or all hydrogen(s) in the alkyl, alkenyl and alkynyl radicals are replaced by fluorine, or one hydrogen is replaced by OH, OC(O)CH
3
, OC(O)H, O—CH
2
—Ph, NH
2
, NH—CO—CH
3
or N(COOCH
2
Ph)
2
), SO
2
—NH
2
, SO
2
NH(C
1
-C
6
)-alkyl, SO
2
N[(C
1
-C
6
)-alkyl]
2
, S—(C
1
-C
6
)-alkyl, S—(CH
2
)
n
-phenyl, SO—(C
1
-C
6
)-alkyl, SO—(CH
2
)
n
-phenyl, SO
2
—(C
1
-C
6
)-alky, SO
2
—(CH
2
)
n
-phenyl (where n is 0-6 and the phenyl radical may be optionally substituted up to two times by F, Cl, Br, OH, CF
3
, NO
2
, CN, OCF
3
, O—(C
1
-C
6
)-alkyl, (C
1
-C
6
)-alkyl or NH
2
), NH
2
, NH—(C
1
-C
6
)-alkyl, N((C
1
-C
6
)-alkyl)
2
, NH(C
1
-C
7
)-acyl, phenyl, biphenylyl, O—(CH
2
)
n
-phenyl (where n is 0-6), 1-or 2-naphthyl, 2-, 3- or 4-pyridyl, 2- or 3-furanyl, 2- or 3-thienyl (wherein the phenyl, biphenylyl, naphthyl, pyridyl, furanyl or thienyl rings may be optionally substituted up to 3 times by F, Cl, Br, I, OH, CF
3
, NO
2
, CN, OCF
3
, O—(C
1
-C
6
)-alkyl, (C
1
-C
6
)-alkyl, NH
2
, NH(C
1
-C
6
)-alkyl, N((C
1
-C
6
)-alkyl)
2
, SO
2
—CH
3
, COOH, COO—(C
1
-C
6
)-alkyl or CONH
2
), 1,2,3-triazol-5-yl (wherein the triazole ring may be optionally substituted in position 1, 2 or 3 by methyl or benzyl), or tetrazol-5-yl (wherein the tetrazole ring to be substituted in position 1 or 2 by methyl or benzyl);
R
1
′ is H, CF
3
, CN, COOH, COO(C
1
-C
6
)alkyl, CONH
2
, CONH(C
1
-C
6
)alkyl, CON[(C
1
-C
6
)alkyl]
2
(C
1
-C
6
)-alkyl, (C
2
-C
6
)-alkenyl, (C
2
-C
6
)-alkynyl, O—(C
1
-C
6
)-alkyl (where one, more than one or all hydrogen(s) in the alkyl, alkenyl and alkynyl radicals are replaced by fluorine, or one hydrogen is replaced by OH, OC(O)CH
3
, OC(O)H, O—CH
2
—Ph, NH
2
, NH—CO—CH
3
or N(COOCH
2
Ph)
2
), SO
2
—NH
2
, SO
2
NH(C
1
-C
6
)-alkyl, SO
2
N[(C
1
-C
6
)-alkyl]
2
, S—(C
1
-C
6
)-alkyl, S—(CH
2
)
n
-phenyl, SO—(C
1
-C
6
)-alkyl, SO—(CH
2
)
n
—phenyl, SO
2
—(C
1
-C
6
)-alkyl, SO
2
—(CH
2
)
n
-phenyl (where n is 0-6 and the phenyl radical may be optionally substituted up to two times by F, Cl, Br, OH, CF
3
, NO
2
, CN, OCF
3
, O—C
1
-C
6
)-alkyl, (C
1
-C
6
)-alkyl or NH
2
), NH
2
, NH—C
1
-C
6
)-alkyl, N((C
1
-C
6
)-alkyl)
2
, NH(C
1
-C
7
)-acyl, phenyl, biphenylyl, O—(CH
2
)
n
-phenyl (where n is 0-6), 1- or 2-naphthyl, 2-, 3- or 4-pyridyl, 2- or 3-furanyl, 2- or 3-thienyl (wherein the phenyl, biphenylyl, naphthyl, pyridyl, furanyl or thienyl rings may be optionally substituted up to 3 times by F, Cl, Br, I, OH, CF
3
, NO
2
, CN, OCF
3
, O—(C
1
-C
6
)-alkyl, (C
1
-C
6
)-alkyl, NH
2
, NH(C
1
-C
6
)-alkyl, N(C
1
-C
6
)-alkyl)
2
, SO
2
—CH
3
, COOH, COO—(C
1
-C
6
)-alkyl or CONH
2
), 1,2,3-triazol-5-yl (wherein the triazole ring may be optionally substituted in position 1, 2 or 3 by methyl or benzyl), or tetrazol-5-yl (wherein the tetrazole ring may be optionally substituted in position 1 or 2 by methyl or benzyl);
R2 is NH
2
, NHR3 or NR4R5, wherein
R3 is (C
1
-C
6
)alkyl, CN, CH═NH, C(═S)—NH
2
, C(═NH)—NH-phenyl (wherein the phenyl ring may be optionally substituted up to two times by F, Cl, Br, I, OH, CF
3
, NO
2
, CN, OCF
3
, O—(C
1
-C
6
)-alkyl, (C
1
-C
6
)-alkyl, NH
2
, NH(C
1
-C
6
)-alkyl, N(C
1
-C
6
)-alkyl)
2
, SO
2
—CH
3
, COOH, COO—(C
1
-C
6
)-alkyl or CONH
2
), phenyl, CH
2
-phenyl (wherein the phenyl ring may be optionally substituted up to 3 times by F, Cl, Br, I, OH, NO
2
, CN, OCF
3
, O—(C
2
-C
6
)-alkyl, (C
2
-C
6
)-alkyl, NH
2
, NH(C
1
-C
6
)-alkyl, N((C
1
-C
6
)-alkyl)
2
, SO
2
—CH
3
, COOH, COO—(C
1
-C
6
)-alkyl or CONH
2
), biphenylyl, 1- or 2-naphthyl, 4-pyridyl, 2- or 3-furanyl, 2- or 3-thienyl, 5-tetrazolyl (wherein the biphenylyl, naphthyl, pyridyl, furanyl or thienyl rings may be optionally substituted up to two times by F, Cl, Br, I, OH, CF
3
, NO
2
, CN, OCF
3
, O—(C
1
-C
6
)-alkyl, (C
1
-C
6
)-alkyl, NH
2
, NH(C
1
-C
6
)-alkyl, N((C
1
-C
6
)-alkyl)
2
, SO
2
—CH
3
, COOH, COO—(C
1
-C
6
)-alkyl or CONH
2
), CH
2
-phenyl, CH
2
-2-pyridyl or CH
2
-4-pyridyl (wherein the phenyl or pyridyl ring may be optionally substituted once or twice by F, Cl, Br, I, OH, CF
3
, NO
2
, CN, OCF
3
, O—(C
1
-C
6
)-alkyl, (C
1
-C
6
)-alkyl, NH
2
, NH(C
1
-C
6
)-alkyl, N(C
1
-C
6
)-alkyl)
2
, SO
2
—CH
3
, COOH, COO—(C
1
-C
6
)-alkyl or CONH
2
);
R4 is C
1
-C
6
-alkyl, C
3
-C
6
-cycloalkyl, C
2
-C
6
-alkenyl, C
3
-C
6
-alkynyl, phenyl, or CH
2
-phenyl (wherein the phenyl ring may be optionally substituted once or twice by F, Cl, Br, I , OH, CF
3
, NO
2
, CN, OCF
3
, O—C
1
-C
6
)-alkyl, C
1
-C
6
)-alkyl, NH
2
, NH(C
1
-C
6
)-alkyl, N((C
1
-C
6
)-alkyl)
2
, SO
2
—CH
3
, COOH, COO—(C
1
-C
6
)-alkyl or CONH
2
); and
R5 is C
1
-C
6
-alkyl, C
3
-C
6
-cycloalkyl, C
2
—C
6
-alkenyl, C
3
-C
6
-alkynyl, phenyl or CH
2
-phenyl (wherein the phenyl ring to be substituted once or twice by F, Cl, Br, 1, OH, CF
3
, NO
2
, CN, OCF
3
, O—C
1
-C
6
)-alkyl, C
1
-C
6
)-alkyl, NH
2
, NH(C
1
-C
6
)-alkyl, N((C
1
-C
6
)-alkyl)
2
, SO
2
—CH
3
, COOH, COO—C
1
-C
6
)-alkyl, or CONH
2
) or
R4 and R5 together form one of the groups CH
2
—CH
2
—CH
2
—CH
2
—CH
2
, CH
2
—CH
2
—N(CH
3
)—CH
2
—CH
2
—CH
2
—CH
2
—N(CH
2
-phenyl)—CH
2
—CH
2
, CH
2
—CH
2
—O—CH
2
—CH
2
, or CH
2
—CH
2
—CH
2
—CH
2
;
and their physiologically tolerated salts and physiologically functional derivatives.
The invention also relates to pharmaceutical compositions containing the compounds of formula I and pharmaceutically acceptable carriers. Also, pharmaceutical compositions containing the compounds of formula I in combination with at least one additional anorectic agents are contemplated. The invention envisages treatment of obesity via administration of compounds of formula I. Methods of treatment for type II diabetes are also contemplated.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
The invention is directed to polycyclic thiazole compounds which are useful in the treatment of type II diabetes and obesity. The compounds have general formula (I):
in which
Y is a direct linkage, CH
2
or CH
2
—CH
2
;
X is CH
2
or O;
R1 is CF
3
, CN, COOH, COO(C
1
-C
6
)alkyl, CONH
2
, CONH(C
1
-C
6
)alkyl, CON[(C
1
-C
6
)alkyl]
2
, (C
1
-C
6
)-alkyl, (C
2
-C
6
)-alkenyl, (C
2
-C
6
)-alkynyl, O—(C
1
-C
6
)-alkyl (where one, more than one or all hydrogen(s) in the alkyl, alkenyl and alkynyl radicals are replaced by fluorine, or one hydrogen is replaced by OH, OC(O)CH
3
, OC(O)H, O—CH
2
—Ph, NH
2
, NH—CO—CH
3
or N(COOCH
2
Ph)
2
), SO
2
-NH
2
, SO
2
NH(C
1
-C
6
)-alkyl, SO
2
N[(C
1
-C
6
)-alkyl]
2
, S—(C
1
-C
6
)-alkyl, S—(CH
2
)
n
-phenyl, SO—(C
1
-C
6
)-alkyl, SO—(CH
2
)
n
-phenyl, SO
2
-C
1
-C
6
)-alkyl, SO
2
—(CH
2
)
n
-phenyl (where n is 0-6 and the phenyl radical may be optionally substituted up to two times by F, Cl, Br, OH, CF
3
, NO
2
, CN, OCF
3
, O—(C
1
-C
6
)-alkyl, (C
1
-C
6
)-alkyl or NH
2
, NH
2
, NH—(C
1
-C
6
)-alkyl, N((C
1
-C
6
)-alkyl)
2
, NH(C
1
-C
7
)-acyl, phenyl, biphenylyl, O—(CH
2
)
n
-phenyl (where n is 0-6), 1- or 2-naphthyl, 2-, 3- or 4-pyridyl, 2- or 3-furanyl, 2- or 3-thienyl (wherein the phenyl, biphenylyl, naphthyl, pyridyl, furanyl or thienyl rings may be optionally substituted up to 3 times by F, Cl, Br, I, OH, CF
3
, NO
2
, CN, OCF
3
, O—C
1
-C
6
)-alkyl, (C
1
-C
6
)-alkyl, NH
2
, NH(C
1
-C
6
)-alkyl, N((C
1
-C
6
)-alkyl)
2
, SO
2
—CH
3
, COOH, COO—(C
1
-C
6
)-alkyl

Affiliated with

Also associated with

Rating

Polycyclic 2- aminothiazole systems, processes for their... does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Polycyclic 2- aminothiazole systems, processes for their..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Polycyclic 2- aminothiazole systems, processes for their... will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-2503356